Microbiology: Antimicrobial Drugs

Chapter 20: Antimicrobial Drugs

Introduction to Antimicrobial Drugs

  • Chemotherapy: The use of chemicals to treat diseases.

  • Selective Toxicity: The ability to find and destroy pathogens without harming the host organism.

  • Antibiotics: Substances produced by microbes that inhibit the growth of other microbes in small amounts.

  • Antimicrobial Drugs: Synthetic substances that interfere with the growth of microbes.

Historical Background of Chemotherapy

  • 1928: Discovery of penicillin by Alexander Fleming, produced by the mold Penicillium.

  • 1932: Introduction of Prontosil, a red dye, used for treating streptococcal infections.

  • 1940: First clinical trials of penicillin, which paved the way for antibiotic therapy.

  • Current Challenge: Increasing problem of antibiotic resistance among bacteria.

Sources of Antibiotics

Table 20-1: Representative Sources of Antibiotics

  • Gram-Positive Rods:

    • Bacillus subtilis: Produces Bacitracin.

    • Paenibacillus polymyxa: Produces Polymyxin.

  • Actinomycetes: Synthesizers of numerous antibiotics including Streptomyces which produces:

    • Streptomyces griseus: Produces Streptomycin.

    • Streptomyces aureofaciens: Produces Chloramphenicol.

    • Saccharopolyspora erythraea: Produces Erythromycin.

Spectrum of Antimicrobial Activity

  • Narrow Spectrum: Drugs that target a limited range of microbes.

  • Broad-Spectrum Antibiotics: Effective against a wide variety of gram-positive and gram-negative bacteria.

  • Superinfection: Occurs when there is an overgrowth of normal microbiota resistant to antibiotics. Examples include Candida albicans and Clostridioides difficile.

Table 20-2: Spectrum of Activity of Antibiotics

  • Prokaryotes:

    • Gram-Negative Bacteria: Includes E. coli, Pseudomonas aeruginosa.

    • Gram-Positive Bacteria: Staphylococcus aureus, Streptococcus pneumoniae.

  • Eukaryotes:

    • Fungi: Candida albicans, Cryptococcus.

    • Protozoa: Giardia intestinalis, Plasmodium (malaria).

    • Viruses: Examples include HIV, influenza.

Mechanisms of Action of Antimicrobial Drugs

Major Types of Action

  1. Bactericidal: Kill microbes directly.

  2. Bacteriostatic: Inhibit the growth of microbes.

Specific Mechanisms of Action

  • Inhibiting Cell Wall Synthesis:

    • Penicillins: Interfere with peptidoglycan synthesis, effective primarily against gram-positive bacteria.

    • Cephalosporins: Similar mechanism to penicillin but with a different beta-lactam structure.

  • Inhibiting Protein Synthesis:

    • Target Bacterial Ribosomes: Apply to 70S ribosomes while human ribosomes are 80S; examples include Streptomycin, Erythromycin.

  • Injuring the Plasma Membrane:

    • Polypeptide Antibiotics: Alter permeability of the membrane, examples include Bacitracin and Polymyxin B.

  • Inhibiting Nucleic Acid Synthesis:

    • Block DNA replication and transcription; key drugs include Quinolones, Rifamycin.

  • Inhibiting the Synthesis of Essential Metabolites:

    • Antimetabolites: Compete with substrates for enzymes. Example: Sulfanilamide competes with para-aminobenzoic acid (PABA).

Antibacterial Drugs Classification

Table 20-3: Antibacterial Drugs by Mode of Action

  • Inhibitors of Cell Wall Synthesis: Includes natural and semisynthetic penicillins, cephalosporins. e.g.,

    • Natural Penicillins: Penicillin G (injection) and Penicillin V (oral).

    • Semisynthetic Penicillins: Ampicillin, Amoxicillin, resistant to penicillinases.

    • Carbapenems: Imipenem, broad spectrum; Monobactams like Aztreonam.

  • Inhibitors of Protein Synthesis: Includes Aminoglycosides, Tetracyclines, Macrolides, etc.

    • Aminoglycosides: Streptomycin, Neomycin, Gentamicin.

    • Tetracyclines: Broad-spectrum; risk of super-infections, act on tRNA.

Antifungal, Antiviral, Antiprotozoan, and Antihelminthic Drugs

Table 20-5: Classification of Drugs

  • Antifungal Drugs:

    • Polyenes (Nystatin, Amphotericin B): Damage membrane sterols.

    • Azoles (Clotrimazole, Ketoconazole): Inhibit ergosterol synthesis.

  • Antiviral Drugs:

    • Nucleoside Analog (e.g., Acyclovir): Block DNA synthesis.

  • Antiprotozoan Drugs:

    • Quinine and Chloroquine used to treat malaria.

  • Antihelminthic Drugs:

    • Niclosamide inhibits ATP production.

Resistance to Antimicrobial Drugs

  • Persister Cells: Microbes resistant to antibiotics due to genetic traits.

  • Superbugs: Antibiotic-resistant bacteria like Acinetobacter baumannii.

  • Mechanisms of Resistance:

    • Enzymatic destruction of drugs (e.g., beta-lactamases).

    • Alteration of drug target sites, e.g., MRSA.

    • Rapid efflux mechanisms that expel antibiotics from bacterial cells.

Antibiotic Misuse and Prevention

  • Common Misuses: Include non-prescription availability, incomplete courses, and inappropriate usage for viral infections.

  • Preventive Measures: Completing prescriptions, avoiding leftovers, and using narrow-spectrum antibiotics.

Future Directions in Antimicrobial Therapy

  • Targeting virulence factors, utilizing bacteriocins, and incorporating phage therapy in clinical settings.